Hydrocephalus is the buildup of fluid (cerebrospinal fluid-CSF) within the ventricular system of the brain, sometimes referred to as “water on the brain.” This is a serious condition that leads to neuronal death and long-term complications. CSF is produced by the choroid plexus (CP) which is an epithelial cell lined tuft of capillaries that project into the ventricles. The ventricle system is composed of four chambers, lateral ventricles (LV) within each of the cerebral hemispheres, the third ventricle connected to the lateral ventricles in the diencephalon (toward the base of the brain) and a fourth ventricle that is connected to the third ventricle by the cerebral aquaduct (of Sylvius). The CSF escapes from the fourth ventricle through three foramen (of Luschka and Magendie) into the subarachnoid space which surrounds the brain. CSF is reabsorbed into the venous blood by arachnoid granulations attached to the superior sagittal sinus which lies just under the cranial skullcap.
The CSF volume in the brain can be increased as a consequence of either: a) production of excess CSF, b) blocking the flow of CSF is (usually at the cerebral aquaduct) or c) insufficient reabsorption into the venous blood. The basic types of hydrocephalus are 1) communicating (that there is no blockage of flow so may be from over production or limited reabsorption) and noncommunicating (there is blockage to flow out of the brain ventricles).
In infants and children who develop hydrocephalus, the cranial sutures have not yet fused, so the cranium enlarges as the ventricles enlarge. In adults with hydrocephalus, the fused nature of the adult cranium results in increased pressure and tissue damage.
TRPV4 is a cilia-associated protein highly expressed in the ventricular system of the brain. TRPV4 (transient receptor potential vanilloid receptor 4) is one member of a large family of cation channels on the plasma membrane of epithelial and endothelial cells and is expressed in the lung, liver, kidney skin, sweat glands and central nervous system. TRPV4 is activated by changes in osmotic balance (hypotonicity) and mechanical stress (pressure) and, when activated, transports Ca2+ into cells. TRPV4 is expressed by the ventricular ependyma of the choroid plexus that is responsible for cerebrospinal fluid (CSF) generation.
Cerebrospinal fluid is produced via an active process of secretion, which is different from the passive diffusion of water-containing fluids in other swelling-producing processes.